ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.2881C>G (p.Gln961Glu) (rs144989330)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000283901 SCV000441094 uncertain significance Nephronophthisis 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000338978 SCV000441095 uncertain significance Renal-hepatic-pancreatic dysplasia 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000403658 SCV000441096 uncertain significance Meckel-Gruber syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000283901 SCV000552114 uncertain significance Nephronophthisis 2017-01-16 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 961 of the NPHP3 protein (p.Gln961Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs144989330, ExAC 0.05%). This variant has been reported in an individual affected with a nephronophthisis-associated ciliopathy, but a second NPHP3 variant was not observed in this individual (PMID: 23188109). This variant is also known as c.2882C>G in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000727224 SCV000582804 uncertain significance not provided 2017-05-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NPHP3 gene. The Q961E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q961E variant is observed in 30/66600 (0.5%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q961E variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727224 SCV000706741 uncertain significance not provided 2017-10-25 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764465 SCV000895530 uncertain significance Renal-hepatic-pancreatic dysplasia 1; Adolescent nephronophthisis; Meckel syndrome type 7 2018-10-31 criteria provided, single submitter clinical testing

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